Myelolactoferrin index (MLF) and myelopoiesis during bacterial infections and malignant diseases.
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Biomedical subjects
Publications and source records attributed to M Thomsen.
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By isoelectrofocusing in agarose, the properdin factor allotype BfF could be split into two subtypes: BfFa with one major cathodic band and BfFb with the same cathodic band but in addition a major anodic band. By scanning, BfFaFb heterozygotes were distinguished from BfFbFb homozygotes by the stronger intensity of the anodic band in the latter. The two subtypes were segregated perfectly with HLA in 40 families and showed different association patterns with HLA markers. BfFa seemed to be linked to B35 while BfFb showed a strong linkage with all the components of the following haplotype: HLA-A29, Cw-, B44, BfFb, C4A3B1, DR7. The frequency of BfFa among BfFS heterozygotes was 41% (46/113) and that of BfFb 59% (67/113).
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In a French family with 2 parents and 5 children a crossing over was found in the HLA region on both of the parental haplotypes of one of the children. The following markers were studied: HLA-A, B, C,DR, DQ(MB), DP(SB), complement allotypes C4 and Bf and glyoxalase I polymorphism. In the third child, the paternal haplotype had a recombination between HLA-A and HLA-C and the maternal haplotype a recombination between HLA-B and complement locus C4. Mixed lymphocyte cultures confirmed the serological findings and non-HLA markers (blood groups and immunoglobulin allotypes) showed no evidence of extrapaternity. The family also demonstrates a probable duplication of the C4B1 gene in one of the paternal haplotypes.
The gene coding for properdin factor Bf is located in the human major histocompatibility complex and is closely linked to the genes coding for the complement components C2 and C4. Recently, by Southern blotting techniques, a restriction fragment length polymorphism was identified using the endonuclease Taq I, which subdivides haplotypes carrying the F allele of factor Bf. The F allotype has also been subdivided at the protein level by isoelectric focusing into two subtypes Fa and Fb. We have investigated the DNA of 41 healthy unrelated individuals with known BfF subtypes using the 2.3 kb factor Bf cDNA probe to determine if there is any correlation between the Taq I polymorphism and F subtype. We have found that in 23 individuals who carried the Fb subtype a 6.6 kb Taq I fragment was present. The remaining 18 individuals carried the Fa subtype and showed only the 4.5 kb Taq I fragment on Southern blotting (P = 10(-12). This striking correlation (r = 1) between the Fb protein and DNA polymorphism is surprising especially as the 4.5 kb and 6.6 kb Taq I fragments overlap the Bf and C2 genes and the polymorphic Taq I site is located within the C2 gene.
An alternative to the well known reversed-phase separations on chemically-bonded phases has been developed. The approach is based on a dynamic modification of bare silica with long chain quaternary ammonium ions. The influence of the concentration and type of the quaternary ammonium ion, the pH value and the ionic strength of the eluent on the selectivity towards test solutes has been investigated. The large number of parameters that can be varied in the system offers numerous possibilities by which the desired selectivity can be attained. Once established, a high degree of reproducibility of the selectivity between solutes is obtained even when using different brands of silica; this is in contrast to the situation when using chemically-bonded phases, such as, for example, different brands of octadecylsilyl-bonded silica materials.
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Two case-histories of patients with full thickness burns covering 60 and 70% of their bodies are presented. In spite of the obligatory increase in the metabolic rate, both patients had a positive nitrogen balance from the very beginning, maintained exclusively by peroral nutrition.
Case histories of two patients admitted to the Burns Unit in 1976 and 1982, with very extensive and very deep burns, are described. The philosophy behind the usual treatment plan of the Unit and the unorthodox ideas that had to be devised in order to treat the 2 patients are described.
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Recently, it has been suggested that in some patients with autoimmune thyroid diseases the tanned red cell (TRC) method for detection of thyroglobulin autoantibodies (TgAb) is negative where TgAb measured by radioimmunoassay (RIA) show positive values. To investigate this further, patients with thyroid diseases, pernicious anaemia and a control group were studied for serum concentrations of TgAb by TRC and by quantitative RIA, calibrated against MRC Standard A65/93. Antibodies for microsomes (MAb) were measured immunofluoretically. There was in all patient groups (Hashimoto's thyroiditis (n = 41), Graves' disease (n = 50), idiopathic myxoedema (n = 12), euthyroid Graves' disease (n = 7), pernicious anaemia (n = 81) a discrepancy between TgAb measured by TRC and RIA, respectively, whereas there was a reasonable correlation between the presence of TgAb by RIA and the presence of MAb. A possible interference from antinuclear antibodies and rheumatoid factors was ruled out. There was no increased frequency of TgAb measured by RIA in the control group. Fractionation of TRC negative sera revealed macromolecular TRC-activity, whereas TgAb positive sera by both methods had almost exclusively RIA and TRC activity corresponding to IgG. Based on these results and others it seems that the TRC method for measurement of serum TgAb is of limited diagnostic value. Furthermore, the TRC method is in many cases not sensitive enough for screening for TgAb prior to measurement of serum Tg, which is of importance as this method shows false values in the presence of TgAb due to methodological interference.
Circulating immune complexes (IC) were determined in sera from 41 patients with Hashimoto's thyroiditis by a polyclonal rheumatoid factor (pRF) assay based on the inhibition of the agglutination of IgG-coated latex particles. Elevated levels of IC were found in 63% (26/41) of the sera. There was a significant correlation (Rho = 0.91, P less than 0.001) between results obtained before and after treatment of sera with dithiothreitol (DTT). By precipitation with 2.5% polyethylene glycol (PEG) before pRF inhibition assay, the activity of IC was found in only 7% (3/41) of the sera. Size chromatography studies of the sera showed the inhibitory activity predominantly in the intermediary region. When found in the IgM-region the activity was not reduced by DTT. By use of a polyethylene glycol complement consumption test (PEG-CC) the occurrence of IC was 10% (4/41). It was not possible to find any correlation between the detectable IC and the presence of microsomal, thyroglobulin, or thyroid-stimulating antibodies. Based on our studies the sizes of IC seemed to be heterogeneously distributed and the majority were not precipitated by PEG (2.5%), final concentration). The antibodies involved in the formation of complexes seemed to be of IgG or IgA classes. HLA-D typing of the patients showed a non-significant association between HLA-Dw5 and low levels of IC while the presence of HLA-Dw4 was significantly associated with a high level of IC (P less than 0.05).
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Forty-one patients with Hashimoto's thyroiditis (HT) and 82 with Pernicious anaemia (PA) were investigated. All 123 patients were HLA-D typed and results correlated to thyroglobulin antibodies (TgAB), microsomal antibodies (MAb), parietal cell antibodies (PCA), circulating immune complexes (IC), and intrinsic factor antibodies (IFA). In PA, TgAb was found less frequently in Dw2 positive patients than in Dw2 negative patients. IFA was rarely found in Dw5 positive PA patients. In HT, patients positive for Dw5 had lower levels of TgAb. IC were present in 67% of patients with HT, but only in 2.5% of patients with PA (p less than 0.01). Dw5 was associated with low levels of IC in HT. In conclusion, HT and PA seem to be related by their association with HLA-D types, but a heterogeneity in the pattern of antibodies and IC could be seen. The organ specific antibodies characteristic for each disease were present in lower levels in patients with Dw5.
Growth and integrity of human prostatic epithelium is strongly dependent upon the adjacent stroma. Furthermore, the human prostate is under the control of sex hormones. Both facts prompted us to compare epithelium with stroma of human benign prostatic hyperplasia (BPH) and normal prostate (NPR) concerning their metabolism, binding and tissue concentrations of androgens and estrogens. In vitro metabolism was analyzed by t.l.c., androgen and estrogen binding sites were determined by a charcoal adsorption technique, androgen and estrogen tissue concentrations were measured by RIA. The main results are--(1) Metabolism: BPH stroma shows 2-3 times higher 5 alpha-reductase activity than epithelium. This high 5 alpha-reductase activity in BPH stroma dictates the differences between unseparated BPH and NPR, in the former the 5 alpha-reductase activity being 2 times higher. The 3 alpha(beta)-hydroxysteroid dehydrogenase (HSDH) activity is more evenly distributed between stroma and epithelium of BPH and NPR. The ratios of 5 alpha-reductase to HSDH activity in the various tissue fractions indicate that the highest enzymatically regulated 5 alpha-dihydrotestosterone (DHT) enrichment must occur in BPH stroma. (2) Tissue concentrations: unseparated BPH contains 2.2 times more DHT than NPR. About 70% of the total DHT content is found in nuclear fractions, whereby the nuclear DHT content of BPH stroma is significantly higher than that of BPH epithelium. In addition, nuclei of BPH stroma contain significantly more estradiol than epithelial nuclei. (3) Binding: the androgen receptor is evenly distributed between epithelium and stroma of BPH, while the estrogen receptor is preferably assayed in BPH stroma. These studies indicate that the BPH stroma is not only a preferential tissue for 5 alpha-reductase activity and DHT enrichment but also for nuclear estradiol accumulation.